Design considerations of polymeric nanoparticle micelles for chemotherapeutic delivery

Ho, Karyn; Shoichet, Molly S.

doi:10.1016/j.coche.2013.01.003

Cited by 16 publications

(3 citation statements)

References 62 publications

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“…MPCbased polymers are thought to possess improved antifouling properties (Lewis 2000) in comparison to PEG-based polymers due to the greater level of hydration reported for MPC, circa 23 water molecules per MPC unit (Goda et al 2006;Morisaku et al 2008), in contrast to circa 3 per PEG unit (Maxfield and Shepherd 1975;Shikata et al 2006). The premise of these biomimetic NIDS being the ability to avoid reticuloendothelial system (RES) clearance (Gref et al 1994), more so if within the 30-100 nm particle diameter size range (Garcia et al 2014), and thus attain sufficiently long systemic circulatory times such that they can harness the enhanced permeability and retention (EPR) effect (Maeda 2001) in order accumulate at tumour sites due to the abnormally leaky vasculature (Takakura et al 1998;Ho and Shoichet 2013). In the case of pH-responsive MPC-DPA (Ma et al 2003;Salvage et al 2005), the PNM would then release the therapeutic cargo in response to the lowered pH environment found in endosomes (Sharma and Sharma 1997) and tumour tissue (Liu et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterisation, and in vitro cellular uptake kinetics of nanoprecipitated poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA) polymeric nanoparticle micelles for nanomedicine applications

Salvage

Smith

et al. 2016

Appl Nanosci

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Nanoscience offers the potential for great advances in medical technology and therapies in the form of nanomedicine. As such, developing controllable, predictable, and effective, nanoparticle-based therapeutic systems remains a significant challenge. Many polymer-based nanoparticle systems have been reported to date, but few harness materials with accepted biocompatibility. Phosphorylcholine (PC) based biomimetic materials have a long history of successful translation into effective commercial medical technologies. This study investigated the synthesis, characterisation, nanoprecipitation, and in vitro cellular uptake kinetics of PC-based polymeric nanoparticle micelles (PNM) formed by the biocompatible and pH responsive block copolymer poly(2-methacryloyloxyethyl phosphorylcholine)- b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA). Atom transfer radical polymerisation (ATRP), and gel permeation chromatography (GPC) were used to synthesise and characterise the well-defined MPC100-DPA100 polymer, revealing organic GPC, using evaporative light scatter detection, to be more accurate than aqueous GPC for this application. Subsequent nanoprecipitation investigations utilising photon correlation spectroscopy (PCS) revealed PNM size increased with polymer concentration, and conferred Cryo-stability. PNM diameters ranged from circa 64–69nm, and increased upon hydrophobic compound loading, circa 65–71nm, with loading efficiencies of circa 60% achieved, whilst remaining monodisperse. In vitro studies demonstrated that the PNM were of low cellular toxicity, with colony formation and MTT assays, utilising V79 and 3T3 cells, yielding comparable results. Investigation of the in vitro cellular uptake kinetics revealed rapid, 1h, cellular uptake of MPC100-DPA100 PNM delivered fluorescent probes, with fluorescence persistence for 48h. This paper presents the first report of these novel findings, which highlight the potential of the system for nanomedicine application development

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Section: Introductionmentioning

confidence: 99%

Synthesis, characterisation, and in vitro cellular uptake kinetics of nanoprecipitated poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA) polymeric nanoparticle micelles for nanomedicine applications

Salvage

Smith

et al. 2016

Appl Nanosci

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“…Multiple synthetic and natural biodegradable polymers may be used in antitumor drug delivery systems, such as polyesters (e.g., polylactic acid, PLA), polyamino acids (e.g., polyaspartic acid), and polyoxypropylenes (e.g., poloxamers) [ 233 ].…”

Section: Nanotechnology-based Drug Delivery Systemsmentioning

confidence: 99%

Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review

Rigon

Oyafuso

Fujimura

et al. 2015

BioMed Research International

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Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

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“…Polymeric micelles have a core-shell structure where the hydrophobic core can load hydrophobic drugs, and the hydrophilic shell introduces colloidal stability and stealth properties to the nanocarrier 7,8 . Important physicochemical characteristics of polymeric micellar formulations affecting their biological destination is the size of this drug carrier [9][10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

The effect of self-assembly conditions on the size of di- and tri-block copolymer micelles: solicitation from response surface methodology

Honary

Lavasanifar

2014

Pharmaceutical Development and Technology

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The objective of this study was to assess the application of Response Surface Methodology in defining the effect of self-assembly condition on the average diameter of polymeric micelles. Di- and tri-block copolymers of poly(ethylene oxide)-b-poly(α-benzylcarboxylate-ϵ-caprolactone) (PEO-PBCL) and PBCL-b-poly(ethylene glycol)-b-PBCL (PBCL-PEG-PBCL) were synthesized through ring opening polymerization of α-benzyl-ε-carboxylate using MePEO or dihydroxy PEG as initiator, respectively. Polymeric micelles were formed through solubilization of block copolymers in acetone followed by drop-wise addition of this solution to water. Polymer concentration was changed and the intensity mean diameter of self-assembled structures was measured by dynamic light scattering. The experimental data were fitted to a mathematical model. The experimental conditions leading to the production of micelles of certain size (30, 60 or 90 nm for tri-block and 30 nm for di-block copolymers) was predicted. A good match between predicted and experimental data was observed. The results showed it would be possible to obtain micelles of certain size using block copolymers of different molecular weights or obtain micelles of different size at a given block copolymer molecular weight, by manipulating the polymer concentration. These observations show reproducible micelles of defined average diameter can be prepared by co-solvent evaporation by controlling the used polymer concentration.

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Design considerations of polymeric nanoparticle micelles for chemotherapeutic delivery

Cited by 16 publications

References 62 publications

Synthesis, characterisation, and in vitro cellular uptake kinetics of nanoprecipitated poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA) polymeric nanoparticle micelles for nanomedicine applications

Synthesis, characterisation, and in vitro cellular uptake kinetics of nanoprecipitated poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA) polymeric nanoparticle micelles for nanomedicine applications

Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review

The effect of self-assembly conditions on the size of di- and tri-block copolymer micelles: solicitation from response surface methodology

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